XANTHINE-OXIDASE AS A SOURCE OF FREE-RADICAL DAMAGE IN MYOCARDIAL ISCHEMIA
XANTHINE-OXIDASE AS A SOURCE OF FREE-RADICAL DAMAGE IN MYOCARDIAL ISCHEMIA
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DOI：
10.1016/s0022-2828(85)80017-1
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发表时间：
1985-01-01
影响因子：
5
通讯作者：
DOWNEY, JM
中科院分区：
文献类型：
--
作者：
CHAMBERS, DE;PARKS, DA;DOWNEY, JM
进行实验以确定黄嘌呤氧化酶是否是心肌缺血期间自由基的来源。开胸犬的左冠状动脉前降支完全闭塞 1 小时，然后再灌注 4 小时。冠状动脉闭塞后，立即将 Ce141 微球注入左心房以标记缺血床。再灌注结束时，取出心脏并切片。放射自显影确定有缺血心肌的风险；通过三苯基四唑染色确定坏死区。将动物分为3组：对照组；别嘌呤醇（24 小时口服预处理 400 mg，然后闭塞时静脉推注 50 mg/kg）；和从闭塞开始的超氧化物歧化酶（15,000 U/kg）。梗塞的大小占危险组织的百分比为：23.1.+-。 4.1 用于控制； 8.7.+-. 1.2 对于别嘌呤醇组；和5.4.+-。 1.2 为超氧化物歧化酶组。别嘌呤醇和超氧化物歧化酶组的梗塞明显小于对照组。在第二系列实验中，测定了狗心肌中黄嘌呤氧化酶/黄嘌呤脱氢酶的含量。左前降支结扎30分钟；从正常区域和缺血区域取出活组织检查。 2 个区域的总酶含量没有差异，缺血组织平均为 0.259 U/g 蛋白质，正常区域为 0.225 U/g 蛋白质。在正常区域，只有9.8%的酶以氧化酶形式存在，而在缺血区域，32.8%的酶以氧化酶形式存在。狗心肌确实含有黄嘌呤氧化酶。该含量随缺血而增加。对该酶的阻断提供了与超氧化物清除剂超氧化物歧化酶相当的保护。
Experiments were performed to determine if xanthine oxidase is a source of free radicals during myocardial ischemia. Open chest dogs were subjected to 1 h of total occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Directly after coronary artery occlusion, Ce141 microspheres were injected into the left atrium to mark the ischemic bed. At the end of reperfusion, the hearts were removed and sectioned. Autoradiography determined the ischemic myocardium at risk; the necrotic zone was determined by triphenyl-tetrazolium staining. Animals were divided into 3 groups: control; allopurinol (24 h oral pretreatment 400 mg, then 50 mg/kg i.v. bolus on occlusion); and superoxide dismutase starting with occlusion (15,000 U/kg). The size of the infarct as a percentage of the tissue at risk was: 23.1 .+-. 4.1 for the control; 8.7 .+-. 1.2 for the allopurinol group; and 5.4 .+-. 1.2 for the superoxide dismutase group. Infarcts in the allopurinol and superoxide dismutase groups were significantly smaller than those in the control groups. In a 2nd series of experiments xanthine oxidase/xanthine dehydrogenase content was determined in dog myocardium. The left anterior descending branch was ligated for 30 min; biopsies were removed from the normal and ischemic regions. Total enzyme content did not differ between the 2 regions averaging 0.259 U/g protein for the ischemic tissue and 0.225 U/g protein for the normal region. Only 9.8% of the enzyme was in the oxidase form in the normal region while 32.8% was in the oxidase form in the ischemic zone. Dog myocardium does contain xanthine oxidase. This content increases with ischemia. Blockade of this enzyme afforded protection comparable to that of the superoxide scavenger superoxide dismutase.